The protean manifestations of GATA2 deficiency across the lifespan
G. Burroughs Mider Lecture | to
Steve M. Holland, M.D.
Chief, Laboratory of Clinical Infectious Diseases
Chief, Immunopathogenesis Section, LCID
National Institute of Allergy and Infectious Diseases (NIAID)
Dr. Holland came to the NIH in 1989 to study the molecular biology of HIV. In 1991, he began studying phagocytes and phagocyte immunodeficiencies. His work centers on understanding the pathophysiology and treatment of infections in patients with congenital and acquired immune defects affecting phagocytes. Areas of interest include mycobacterial infections (interferon gamma/IL-12 pathway defects, anticytokine autoantibodies, GATA2), hyper IgE syndrome (STAT3, DOCK8), and chronic granulomatous disease.
GATA binding factor 2 (GATA2) was initially cloned in 1991 as a critical regulator of murine endothelial development, the complete absence of which was incompatible with life. Subsequent work confirmed that it was also critical for hematopoiesis, erythropoiesis, and macrophage function. After almost 20 years of characterization of patients with disseminated mycobacterial infections who had monocytopenia, B cell and NK (natural killer) cell cytopenia, Steve Holland’s group found heterozygous mutations in the same transcription factor, GATA2, accounting for their disease. However, in humans these heterozygous mutations cause haploinsufficiency and underlie myelodysplasia, myeloid leukemia, pulmonary alveolar proteinosis, classical NK cell deficiency, and lymphedema. GATA2 deficiency causes a late onset congenital immunodeficiency that can be cured by bone marrow transplantation. GATA2 is involved in many processes with virtually complete penetrance but highly variable expression, suggesting that genetic and epigenetic modifiers are important.
This page was last updated on Wednesday, August 11, 2021